Randomized. 1485 pts. Randomized to RT with 5 fractions per week (overall treatment time: 46 days) vs 6 fractions per week (39 days), but with the same total dose and same number of fractions (66-68 Gy in 33-34 fx). The 6th fraction was given either on a weekend or during the week as a 2nd daily fraction (>6 hrs interval). Pts recd hypoxic radiosensitizer nimorazole (except those with glottic ca).

DAHANCA 6 & 7 are subprotocols. DAHANCA 6 was for glottic tumors only. Nimorazole was not given. DAHANCA 7 included SGL, pharynx, and OC, and nimorazole was given. All other aspects of the trials were the same.

Conclusion: Quality adjusted survival better only for hyperfractionated fractionation, not for accelerated. Q-TWiST analysis can identify patient groups that would benefit from more aggressive therapy based on their utilities

Phase III. 840 pts. Stage II-IV (OC, OP, L, HP). When given, chemotherapy was three cycles of 4 days of carboplatin 70 mg/m2 per day plus fluorouracil 600 mg/m2 per day for days 1-4 (conventional) or days 1-5 (accelerated)

RT options: 1) 70 Gy in 7 weeks (five fractions of 2 Gy per week) with spinal cord exclusion at 40 Gy and chemotherapy of three cycles; 2) 70 Gy in 6 weeks: five fractions of 2 Gy per week until 40 Gy (with spinal cord exclusion at 40 Gy) and then 1.5 Gy per fraction twice daily for 5 days per week for the remaining 30 Gy and concomitant chemotherapy of two cycles; 3) 64.8 Gy in 3.5 weeks without chemotherapy (1.8 Gy twice daily for five days per week), with spinal cord exclusion at 34.2 Gy.

RT Methods: 3D conformal; IMRT not allowed; Cervical posterior nodes were treated with electron beams (8–12 MeV) or with oblique posterior photon beams. The prophylactic nodal irradiation dose was 45 Gy in the uninvolved neck in the very accelerated radiotherapy group and 50 Gy for the two other groups.

Authors' Conclusions: Chemotherapy has substantial treatment effect given concomitantly with RT and accelerated RT cannot compensate for the absence of chemotherapy. Best Outcomes were in conventional chemoradiotherapy arm, suggesting that acceleration of radiotherapy is probably not beneficial in concomitant chemoradiotherapy schedules.

Editorial: Contrary to the main hypothesis to the trial, there was no benefit for accelerated RT with respect to PFS ([HR] 1.02, 95% CI 0.84–1.23; p=0.88), overall survival (1.05, 0.86–1.29; p=0.60), locoregional failures (0.97, 0.74–1.26; p=0.81), or distant metastases (1.26, 0.90–1.75; p=0.18). This corroborates results from RTOG 0129, which failed to demonstrate a survival advantage of accelerated-fractionation RT compared with standard-fractionation combined with concurrent carboplatin. In this trial, very accelerated RT (without chemotherapy) resulted in more frequent acute grade 3–4 mucosal toxic effects, a higher proportion of PEG-dependency, and inferior PFS and OS than did conventional chemoradiotherapy. From these results, it seems safe to conclude that with 2D/3D fields, the addition of chemotherapy to conventional RT compensates for a potential benefit from acceleration of radiotherapy.

Strengths: With 840 patients randomly allocated during more than 7 years, GORTEC 99-02 was the largest randomized study to assess the potential benefit of combination of different intensification strategies to date.